Inflammatory neuropathies with paranodal antibodies: more than just IgG


In the last five years exciting discoveries have been made regarding the role of different antibodies in inflammatory neuropathies. Specifically, patients with IgG-autoantibodies against paranodal proteins (e.g. contactin-1 or neurofascin-155) have a specific clinical phenotype characterized by a subacute motor predominant neuropathy, which tend to be refractory to intravenous immunoglobulins (IVIG) but may respond to steroids or rituximab. However, other subclasses of immunoglobulins, such as IgA and IgM, have not been systematically explored so far.

In the November issue of JNNP, Doppler and colleagues explore the prevalence of IgM antibodies against neurofascin-155, neurofascin-186, and contactin-1 in a cohort of patients negative for IgG antibodies and with the diagnosis of inflammatory neuropathies. After screening 140 patients, IgM autoantibodies against neurofascin-155 were detected in five patients (four with CIDP and one with GBS). No patients tested positive for IgM against contactin-1 and neurofascin-186. From a clinical point of view, patients IgM (+) presented with a distal quadriparesis and distal hypesthesia. Tremor was present in 4 out of 5 patients. Most of the patients have a good response to IVIG.


Figure 1. IgM autoantibodies against neurofascin-155 in inflammatory neuropathies. A. Nodal and paranodal regions. B. T cell around epineural vessels in a patient with IgM autoantibodies.


Even though the pathogenic role of IgM antibodies against neurofascin-155 has not been established, this study highlights the large clinical and immunological heterogeneity across CIDP patients and the potential role of IgM antibodies in inflammatory neuropathies. Of relevance, patients with IgM antibodies appear to have a good response to IVIG, a distinctive feature from patients with IgG4 autoantibodies against paranodal proteins. Since early effective treatment is crucial in preventing axonal loss and disability, further studies should address the diagnostic and prognostic role of IgM autoantibodies, furthering progress into a personalized medicine in the field of inflammatory neuropathies.







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